Applying Efficient Implicit Nongeometric Constraints in Alchemical Free Energy Simulations

作者：Knight Jennifer L^*; Brooks Charles L III

来源：Journal of Computational Chemistry, 2011, 32(16): 3423-3432.

DOI：10.1002/jcc.21921

• theta-dynamics
• lambda-dynamics
• constraint

Several strategies have been developed for satisfying bond lengths, angle, and other geometric constraints in molecular dynamics simulations. Advanced variations of alchemical free energy perturbation simulations, however, also require nongeometric constraints. In our recently developed multisite lambda-dynamics simulation method, the conventional lambda parameters that are associated with the progress variables in alchemical transformations are treated as dynamic variables and are constrained such that: 0 < lambda(i) < 1 and Sigma(N)(i=1) lambda(i) = 1. Here, we present four functional forms of lambda that implicitly satisfy these nongeometric constraints, whose values and forces are facile to compute and that yield stable simulations using a 2 fs integration timestep. Using model systems, we present the sampling characteristics of these functional forms and demonstrate the enhanced sampling profiles and improved convergence rates that are achieved by the functional form: lambda(i) = e(i)(csin theta)/Sigma(N)(i=1) e(j)(csin theta) that oscillates between lambda(i) = 0 and lambda(i) = 1 and has relatively steep transitions between these endpoints.

• 出版日期2011-12